Project Summary Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by impairments in social interaction and communication, as well as the presence of repetitive behaviors and restricted interests. Given that an estimated 1 in 68 children have ASD, and the high personal and societal costs associated with caring for individuals with ASD, understanding the neurobiological underpinnings of ASD is an important public health concern. It has been suggested that individuals with ASD are less able than typically-developing (TD) individuals to predict events and optimize behavior based on these predictions. Here, I propose to test the hypothesis that adults with ASD show reduced neural adaptation across multiple domains. Neural adaptation could be a mechanism that supports prediction by differentiating between familiar and novel events. Recent evidence suggests that other neurodevelopmental disorders such as dyslexia are characterized by broad reduction in neural adaptation and in ASD reduced neural adaptation is associated with increased symptom severity. An inability to adapt to a range of stimuli might have knock-on effects on social interaction, communication, and motor behaviors. However, until this point no one has examined the specificity of neural adaptation in ASD, and it is not known whether reduced neural adaptation is the result of bottom-up stimulus- driven adaptation or top-down expectancy. I will recruit 20 TD adults, 20 age-matched adults with ASD, and a small group of 8 children with ASD for a neural adaptation functional magnetic resonance imaging (fMRI) study in which I will test the scope and limits of neural adaptation deficits across multiple domains in ASD. In a second experiment, I will recruit an additional 20 TD adults and 20 age-matched adults with ASD to probe the mechanism of reduced neural adaptation in ASD, and to determine in a second, independent cohort of participants if results of the first experiment replicate despite heterogeneity in ASD. Lastly, I will examine the dimensional relationship of neural adaptation to ASD traits continuously across participants. This work is important as neural adaptation impairments are thought to contribute to multiple psychiatric and neurodevelopmental disorders, including schizophrenia and dyslexia. Knowledge gained from this project will provide a better understanding of the neural underpinnings of neural adaptation in ASD, and potentially inform future neurobiological-based therapeutic treatments for ASD symptoms and other neurodevelopmental disorders.